JP7789744B2 - Process for producing omega bromoalkanoic acids and esters - Google Patents

Description

The present patent application relates to a process for the continuous production of ω-bromoalkanoic acids and esters by hydrobromination reactions . The present invention also relates to a process for the production of aminocarboxylic acids and esters and polyamides or copolyamides from said ω-bromoalkanoic acids or esters.

ω-bromoalkanoic acids or esters, in particular of the following formula (II):
Br-(CH ₂ ) _n+2 -COOR (II)
are advantageous precursors in the polymer industry. In particular, they constitute intermediates for the amino acids and amino esters necessary for the production of polyamides. 11-Bromoundecanoic acid is therefore a precursor for 11-aminoundecanoic acid, which is used on an industrial scale for the production of polyamide 11.

These compounds have the formula (I):
CH ₂ =CH-(CH ₂ ) _n -COOR (I)
wherein n is an integer between 7 and 9, and R is selected from H or a linear or branched alkyl group containing 1 to 10 carbon atoms. The hydrobromination reaction is carried out by adding anti-Markovnikov HBr to the compound of formula (I) in the presence of a radical initiator and one or more solvents.

Although it is possible to carry out the hydrobromination in batch mode, this requires repeated intervention, recovery of residual gaseous HBr is difficult, and the reaction is highly exothermic and therefore difficult to control, therefore the hydrobromination is generally carried out continuously.

Older patent FR928265 describes the continuous hydrobromination of 10-undecenoic acid in a column maintained at a temperature of 30° C., through which a solution of 10-undecenoic acid in toluene is passed and through which excess HBr and air flow countercurrently. This method works well, but produces approximately 20% 10-bromoundecanoic acid, which significantly limits the yield.

Semionov et al. provide such a method with significantly higher yields (>90%), in which the reaction is carried out in toluene in a plug flow reactor at temperatures between 0 and 5°C (Maslozhirova Promyshlennost, 1971, Vol. 37, pp. 31-33). Because the reactor is cooled to very low temperatures, this method is not very energy efficient and requires a large capital investment.

Patent CN 103804209B describes the continuous hydrobromination of 10-undecenoic acid in a system of two stirred reactors in series. The injection is carried out from a mixture of 10-undecenoic acid in toluene and benzene, 1% to 5% by weight of azobisisobutyronitrile or benzoyl peroxide as a radical initiator, and HBr in the first stirred reactor, maintained at a temperature of 10 to 30°C, with a residence time of 30 to 90 minutes. The reaction medium from the first reactor is continuously withdrawn and injected into a separation device heated to 65 to 80°C. The residual HBr released in gas form is returned to the first reactor. The maximum yield shown is 92.1%. This method requires a long residence time for a moderate yield. Furthermore, the large amount of radical initiator can be a source of difficult-to-manage residues in the product.

All of these continuous processes operate using benzene, a carcinogenic and mutagenic solvent, and/or toluene, a solvent that can produce benzyl bromide, a lachrymatory compound.

In fact, there is now an increasing goal to replace benzene and toluene with other solvents that have a more favorable toxicity profile or produce fewer by-products.

Patent EP 3030543 B1 provides a continuous hydrobromination process for 10-undecenoic acid, which allows at least partial replacement of benzene with cyclohexane and/or methylcyclohexane. In this process, 10-undecenoic acid is reacted with HBr in liquid form. This document teaches that carrying out the process in a countercurrent column with solvent modification results in a yield loss, which can be compensated for if two consecutive reactors are used, the first with turbulent flow and the second with laminar flow. This process has the disadvantage of requiring HBr in liquid form, which results in restrictions on HBr purity and significant energy consumption and capital costs, since HBr or the HBr solution must be cooled to temperatures significantly below 0°C to ensure sufficient HBr solubility.

It is therefore an object of the present invention to provide a process for the continuous synthesis of ω-bromoalkanoic acids and esters by hydrobromination reaction without the use of benzene and/or toluene, which process shows a satisfactory yield of the product of formula (II), preferably of at least 92%, in particular of at least 94%.

According to one embodiment, the object of the present invention is to provide a continuous synthesis method that saves energy and in particular does not require high pressure or temperatures below 5°C.

According to another embodiment, it is an object of the present invention to provide a continuous synthesis method that allows the use of HBr contaminated with hydrogen, HCl, or water.

According to another embodiment, the object of the present invention is to provide a continuous synthesis method that allows for a reduction in the amount of HBr introduced into the method, a compound that is expensive to produce and remove.

According to yet another embodiment, the object of the present invention is to provide a continuous synthesis method with reduced residence times, in particular less than 30 minutes, and especially less than 15 minutes.

In another embodiment, the object of the present invention is to provide a continuous synthesis method that allows for the production of compounds of formula (II) that are free or substantially free of impurities.

In another embodiment, an object of the present invention is to provide a continuous synthesis method that does not require solid radical initiators, which are reagents that pose a risk of violent decomposition reactions.

In another embodiment, the object of the present invention is a method for producing an aminocarboxylic acid or ester from a compound of formula (II).

Finally, according to another embodiment, the object of the present invention is a method for producing a polyamide or copolyamide from a compound of formula (II).

Indeed, the present invention is based on the observation that it is possible to replace benzene and toluene with aliphatic solvents in the continuous production of ω-bromoalkanoic acids and esters by hydrobromination reactions while maintaining high yields under conditions that ensure a sufficient molar excess of HBr in the reaction.

To obtain a high yield of the compound of formula (II), it is important to properly control the thermal conditions, as high temperatures promote the appearance of entities without bromine at the chain ends.

Thus, according to a first aspect, the subject of the present invention is a method for the continuous synthesis of compounds of formula (II) Br—(CH ₂ ) _n+2 —COOR, comprising:
(a) hydrobromination of a compound of formula (I) CH ₂ ═CH—(CH ₂ ) _n —COOR with HBr in the presence of a radical initiator and at least one solvent,
In formulae (I) and (II), n is an integer between 7 and 9, and R is selected from H or a linear or branched alkyl group containing 1 to 10 carbon atoms, in particular methyl, ethyl, isopropyl or propyl;
The process is characterized in that the reaction is carried out in the absence of benzene and toluene, and in step (a) HBr is injected into the reaction mixture in gaseous form and in a stoichiometric excess.

Advantageously, the ratio of the molar flow rate of HBr injected in step (a) to the molar flow rate of the compound of formula (I) injected in step (a) is between 1.2 and 3, preferably between 1.3 and 2.2, more preferentially between 1.4 and 2, in particular between 1.5 and 1.9.

According to one embodiment, the outlet stream of liquid reaction mixture from the reactor at the end of step (a) contains at least 2% by weight, preferably at least 3% by weight, more preferentially at least 3.5% by weight, in particular at least 4% by weight, of HBr.

Preferably, the method of the present invention comprises:
(b) separating excess HBr from the liquid reaction mixture resulting from step (a);
(b1) optionally further comprising the subsequent steps of separating excess HBr from the gaseous reaction mixture resulting from step (a), and (c) recycling the excess HBr separated in step (b) and, where appropriate, step (b1) to step (a).

Advantageously, the method of the invention comprises the steps of:
(a1) introducing into a first reactor at a suitable temperature and for a suitable residence time the compound of formula (I), HBr, an initiator and a solvent; and (a2) withdrawing the reaction mixture from the first reactor and introducing it into a separation device, where appropriate:
followed by the subsequent steps of (b) separating residual HBr from the reaction mixture, and (c) recycling the separated HBr to step (a1).

Step (a) can be carried out in a reaction medium saturated with HBr. It can be carried out at a temperature between 5°C and 50°C, preferably between 10°C and 40°C, and especially between 20°C and 30°C.

The radical initiator can be molecular oxygen, used neat or as a mixture with an inert gas, such as air or oxygen-enriched air.

The first reactor may be, in particular, a stirred vessel equipped with a self-priming turbine or a jet loop reactor equipped with a venturi. The separation device may, in particular, be a stirred vessel or a column.

Advantageously, the process according to the present invention is carried out in the absence of an aromatic solvent.

The product of formula (I) can be selected from 11-bromoundecanoic acid, 10-bromodecanoic acid, and 9-bromononanoic acid.

The solvent can be selected from cyclohexane, methylcyclohexane, methylcyclopentane, n-hexane, 2-methylhexane, 3-methylhexane, n-heptane, isooctane, petroleum ether, tetralin, 1,1,1-trichloroethane, dibromoethane, chloroform, carbon tetrachloride, tetrachloroethylene, 1-bromopropane, dimethyl carbonate, tetrahydrofuran, 1,4 dioxane, 2-methyltetrahydrofuran, tetrahydropyran, 1-propoxypropane, 1-ethoxybutane, 2-isopropoxypropane, acetonitrile, and mixtures thereof.

According to another aspect, the present invention provides a method for the synthesis of a compound of formula (III) NH ₂ —(CH ₂ ) _n+2 —COOR, comprising:
(i) ammonolysis of the compound of formula (II) obtained by the above process, and (ii) isolation of the compound of formula (III) NH ₂ —(CH ₂ ) _n+2 —COOR formed.

Finally, in another aspect, the present invention relates to a method for synthesizing polyamides or copolyamides, comprising the step of polycondensing the compound of formula (III) obtained by the above method, either alone or in a mixture with other monomers.

A better understanding of the present invention can be obtained in light of the following description and drawings.

1 is a diagram of an installation for carrying out a method according to one embodiment of the present invention; 1 is a diagram of an installation for carrying out a method according to one embodiment of the present invention, comprising a venturi and an external heat exchanger; FIG. 1 is a diagram of an installation for carrying out a method according to an embodiment of the present invention, comprising a venturi;

Definition of Terms In the context of the present disclosure, the term "stoichiometric excess in the context of a continuous process" is understood to mean a molar flow rate of a reactant that is greater than the molar flow rate required for the envisaged reaction. For example, 1 mole/hour of HBr is required to carry out 1 mole/hour of the hydrobromination reaction of a compound of formula (I). Thus, a ratio of molar flow rate of HBr/molar flow rate of the compound of formula (I) > 1 constitutes a stoichiometric excess of HBr.

In the context of the present disclosure, the term "residence time" is understood to mean the ratio of the volume occupied by the liquid reaction mixture to the sum of the flow rates in volume units of the compound of formula (I) and the solvent introduced into the process.

In the context of the present disclosure, the term "ω-bromoalkanoic acid or ester" is understood to refer to an alkanoic acid or ester having at least one bromine atom on a terminal carbon atom. ω-alkanoic acids or esters having a straight chain are preferred.

The method of the present invention is particularly directed to the reaction of a compound of formula (II):
Br-(CH ₂ ) _n+2 -COOR (II)
wherein n is an integer between 7 and 9, and R is selected from H or a linear or branched alkyl group containing 1 to 10 carbon atoms, in particular methyl, ethyl, isopropyl, or propyl.

This method is particularly advantageous for producing 12-bromododecanoic acid, 11-bromoundecanoic acid, and 10-bromodecanoic acid.

Compounds of Formula (I) The ω-bromoalkanoic acid or ester of formula (II) is a compound of formula (I):
CH ₂ =CH-(CH ₂ ) _n -COOR (I)
wherein n is an integer between 7 and 9 and R is selected from H or a linear or branched alkyl group containing 1 to 10 carbon atoms, in particular methyl, ethyl, isopropyl or propyl, of a terminally unsaturated carboxylic acid or ester of the formula:

The compound of formula (I) is preferably 10-decenoic acid, 11-undecenoic acid, or 12-dodecenoic acid, or one of their esters, in particular the methyl, ethyl, isopropyl, or propyl esters.

These compounds are commercially available or can be synthesized using conventional organic chemistry reactions. Some of these compounds can be obtained from sustainable starting materials due to their plant origin. Thus, 11-undecenoic acid is advantageously derived from castor oil, as described in particular in FR952985.

The compound of formula (I) is preferably used either in molten form or in liquid form in solution in a suitable solvent.

Advantageously, the compound of formula (I) is used at a temperature of 10 to 70°C, in particular 20 to 50°C.

HBr
HBr may be commercially available, or may be produced by the reaction of bromine with hydrogen, or may be a by-product of another reaction, for example the bromination of aromatic compounds. When the process of the present invention is used for the production of aminocarboxylic acids from ω-bromoalkanoic acids, in particular for the production of polyamides, HBr is advantageously
(i) reacting an ω-bromoalkanoic acid with ammonia in an aqueous solution to form a reaction mixture comprising the corresponding ω-aminocarboxylic acid and ammonium bromide;
(ii) separating the ω-aminocarboxylic acid and the aqueous ammonium bromide-rich solution from the reaction mixture;
(iii) contacting the resulting ammonium bromide-rich aqueous solution with sodium hydroxide to form ammonia and a sodium bromide-rich aqueous solution;
(iv) purifying the resulting sodium bromide-rich aqueous solution to remove organic impurities;
(v) contacting the resulting purified aqueous sodium bromide-rich solution with chlorine to form bromine and an aqueous sodium chloride-rich solution; and (vi) reacting the resulting bromine with hydrogen to form hydrogen bromide.

While HBr may be used pure, one advantage of the method of the present invention is that it also allows for its use in a mixture with other gases, such as hydrogen, HCl, carbon dioxide, or water. Generally, the total content of HBr in other gases is still less than 30 mol %, preferably less than 20 mol %, and in particular less than 10 mol %, relative to HBr. Furthermore, the water content of HBr is preferably less than 3 mol %, preferably less than 1 mol %, relative to HBr.

According to the present invention, HBr is introduced into the reaction mixture of step (a) in gaseous form. Nevertheless, HBr can be partially or completely dissolved in the reaction medium containing the compound of formula (I), the solvent, and also the product of formula (II), which reaction medium is generally in liquid form.

The flow rate of HBr injected into the reaction mixture in step (a) is the sum of the HBr introduced into the process and, where appropriate, recycled HBr.

The present inventors have found that the selectivity and, for this reason, the yield of the hydrobromination reaction is enhanced in the presence of a large amount of HBr dissolved in the reaction medium, obtained by injecting a large stoichiometric excess of HBr into the reaction medium.

According to the process of the present invention, the ratio of the molar flow rate of HBr injected into the reaction mixture in step (a) to the compound of formula (I) injected in step (a) is generally 1.2 to 3, preferably 1.3 to 2.2, more preferentially 1.4 to 2, in particular 1.5 to 1.9. Here and below, the molar ratio of pure HBr to the compound of formula (I) is meant to exclude any other gases or humidity that may be present.

Once injected into the reaction mixture, HBr can dissolve in the reaction mixture and become available for the targeted reaction. HBr that exceeds its solubility in the reaction mixture or that cannot be dissolved in the reaction medium can be vented from the reactor in gaseous form, particularly to adjust the pressure.

In addition, some of the other gases introduced with the HBr that did not dissolve in the reaction medium may also be vented from the reactor.

Advantageously, any HBr not consumed by the reaction remains in the reaction mixture as residual HBr and can then be discharged in this form. Advantageously, the outlet stream of liquid reaction mixture from the reactor contains at least 2% by weight, preferably at least 3% by weight, more preferentially at least 3.5% by weight, and in particular at least 4% by weight, of HBr, based on the weight of the liquid outlet stream from the reactor.

This is because it was found that under these conditions the yield of the compound of formula (II) was maximized.

As described in more detail below, residual HBr can be recycled after being separated from the liquid reaction mixture withdrawn from the reactor. Similarly, a portion of the HBr discharged from the reactor can be recycled in gaseous form.

The amount of recycled HBr can vary depending on the molar ratio of the total HBr injected into the reaction medium, depending on the gas/liquid transfer, and, where appropriate, depending on the separation conditions of the reaction mixture. Preferably, the recycled HBr has a molar ratio with the compound of formula (I) greater than 0.2 and less than 1.5. Generally, this molar ratio is between 0.3 and 1, preferably between 0.4 and 0.9, and more preferably between 0.5 and 0.8.

When the process of the present invention is carried out with HBr recycling, the HBr introduced into the process is preferably injected in stoichiometric excess, thus exhibiting a molar ratio with the compound of formula (I) of greater than 1. Generally, this molar ratio is 1.01 to 1.5, preferably 1.02 to 1.4, more preferentially 1.03 to 1.3, in particular 1.03 to 1.2.

The inventors have discovered that the use of HBr recycle allows for increased selectivity and yield while minimizing HBr consumption and the release of excess HBr into the environment.

Several means make it possible to adjust the flow rate of residual HBr in the liquid outlet stream from the reactor.

The flow rate can be determined by conventional analytical means for HBr, in particular by silver salt analysis, acid-base titration, or ion chromatography.

If the residual HBr content in the liquid outlet stream from the reactor is determined to be too low, the flow rate of HBr introduced into the process can be increased.

Alternatively, if the liquid phase containing compound (II) after the HBr separation step described below contains more than 0.1 wt. % HBr, the flow rate of recycled HBr can be increased by improving the separation conditions for the residual HBr during the HBr separation step, for example by increasing the temperature of the HBr separation step, as described below.

In a particular embodiment of the present invention, the stoichiometric excess of HBr in the reaction medium of step (a) is ensured by monitoring the flow rate of HBr exiting the reactor in gaseous form. This monitoring can be carried out, for example, by measuring the total gas flow exiting the reactor and the HBr concentration in this gas. The ratio of the gaseous molar flow rate of HBr exiting the reactor to the gaseous molar flow rate of HBr introduced into the reactor is preferably between 0.01 and 0.5, more preferentially between 0.02 and 0.4, more preferentially between 0.03 and 0.3, and in particular between 0.03 and 0.2.

Solvents According to the present invention, the process does not use benzene or toluene.

In general, suitable solvents for the process of the present invention are inert organic solvents in which the compound of formula (I) and the reaction product of formula (II), as well as HBr, are soluble at the reaction temperature.

Suitable solvents may be selected from aliphatic or cycloaliphatic compounds, in particular straight- or branched-chain alkanes containing 1 to 10 carbon atoms and, where appropriate, substituted with one or more halogen atoms, in particular bromine or chlorine atoms, alkoxy groups, or nitrile groups; alicyclic compounds, in particular cycloalkanes containing a ring of 4 to 8 carbon atoms, in particular optionally substituted and/or interrupted by one or more oxygen atoms. Some solvents may be esters, in particular carbonate esters.

Among suitable solvents, mention may be made in particular of cyclohexane, methylcyclohexane, methylcyclopentane, n-hexane, 2-methylhexane, 3-methylhexane, n-heptane, isooctane, petroleum ether, tetralin, 1,1,1-trichloroethane, dibromoethane, chloroform, carbon tetrachloride, tetrachloroethylene, 1-bromopropane, dimethyl carbonate, tetrahydrofuran, 1,4-dioxane, 2-methyltetrahydrofuran, tetrahydropyran, 1-propoxypropane, 1-ethoxybutane, 2-isopropoxypropane, acetonitrile, fluorobenzene, chlorobenzene, trifluorotoluene, ethylbenzene, o-xylene, m-xylene, p-xylene, and mixtures thereof.

In the method of the present invention, benzene is not used because it is a carcinogenic and mutagenic product, and toluene is not used because toluene can form benzyl bromide, which is a strong lachrymator and difficult to separate from the reaction products and solvent.

Advantageously, the method does not use solvents and/or aromatic solvents that present HSE problems.

Preferably, the solvent used is selected from cyclohexane, methylcyclohexane, methylcyclopentane, 2-methylhexane, 3-methylhexane, n-heptane, isooctane, petroleum ether, and mixtures thereof. Cyclohexane and methylcyclohexane are particularly preferred.

The flow rate ratio by weight of the compound of formula (I) to the solvent involved in the process can vary widely and can be determined by routine testing according to the process conditions. As a general rule, a flow rate ratio by weight of the compound of formula (I) to the solvent involved in the process of 1:1 to 1:20, preferably 1:2 to 1:10, and especially 1:3 to 1:6, is suitable. It is generally preferable to work under concentrated conditions to optimize productivity. Nevertheless, it is preferred that the amount of solvent be sufficient to prevent crystallization of the compound of formula (I) or (II), especially during the reaction stage.

The solvents involved in the process can be injected into the reaction medium separately or in a mixture with compound (I).

Advantageously, the solvent injected into the reaction medium contains recycled HBr, as described below.

Radical Initiators
The hydrobromination reaction generally requires the presence of a radical initiator.

The radical initiator can be selected from, for example, oxygen, oxygen-containing gases such as air, peroxides such as benzoyl peroxide, diazo compounds such as azobisisobutyronitrile, or any other radical generator such as ultraviolet light.

Molecular oxygen or oxygen-containing gases, such as air or oxygen-depleted air, constitute preferred radical initiators because they are readily available, inexpensive, produce little or no residue in the product, and present no storage stability problems.

The amount of radical initiator used is that conventionally used.

When the radical initiator is a peroxide or diazo compound, it can be used in an amount between 0.1% and 4% by weight, based on the weight of the compound of formula (I).

When oxygen or an oxygen-containing gas is used as the radical initiator, its amount, expressed as the molar ratio between oxygen and the amount of HBr introduced into the process (thus excluding any recycled HBr), may vary in particular between 1:5000 and 1:50, preferably between 1:1000 and 1:200.

Equipment and Process Conditions Step (a) of the hydrobromination reaction of the process of the present invention can be carried out very simply by sequentially contacting a compound of formula (I) with HBr in the presence of a radical initiator and one or more solvents.

Given the gaseous form of HBr, the step is advantageously carried out in a reactor that facilitates gas/liquid material transfer. Such a reactor can be based on a column, such as, for example, a spray column, a falling film column, a bubble column, an ejector column, a mechanically stirred column, a countercurrent or cocurrent packed column, or a perforated plate column.

Alternatively, the reactor may be a stirred vessel-based reactor equipped with, for example, a turbine mixer or a venturi ejector.

Finally, the reactor may be a loop reactor (jet loop reactor), fitted, if appropriate, with a jet nozzle or venturi ejector. This type of reactor comprises a vessel from which a pump continuously withdraws the liquid reaction medium, optionally including a gas fraction in the form of bubbles, in order to return the liquid reaction medium to an ejector connected to a gas stream of HBr injected into the reaction medium. In the ejector, the liquid reaction mixture is ejected at high velocity, dispersing the gas stream of HBr in the form of fine bubbles into the reaction medium. The output from the ejector is sent to the vessel. Preferably, a tube connects the gas phase of the vessel with the gas inlet of the ejector.

Preferably, the hydrobromination reaction step is carried out in a turbine stirred vessel or in a jet loop reactor, especially a jet loop reactor equipped with a venturi ejector.

temperature
The temperature of the reactor during the hydrobromination reaction step is preferably set above the crystallization temperature of the reactants and product. Furthermore, in order to limit energy consumption, it is preferable to select a temperature that is not too low. In order to ensure good selectivity, it is preferable to select a temperature that is not too high. In general, the temperature during the reaction step is preferably 5 to 50°C, preferably 10 to 40°C, in particular 20 to 30°C.

The hydrobromination reaction of the compound of formula (I) is highly exothermic. To ensure good selectivity, it is advantageous to connect the reactor to a heat exchanger. Such devices are known to those skilled in the art and can be, for example, a jacket around the reactor, or a device arranged on an external loop, or a device arranged inside the reactor. Preferably, the heat exchanger is arranged on an external loop outside the reactor. In this case, the liquid reaction medium is continuously withdrawn from the reactor, sent to an external exchanger, and then returned to the reactor. Any type of heat exchanger can be envisaged, such as a tube or plate exchanger.

According to a particular embodiment of the present invention, it is possible to use a packed column in which the solvent and reactant (I) are injected at the top, HBr and the radical initiator are injected at the bottom, and a portion of the liquid reaction medium is withdrawn at the bottom of the column, pumped to a heat exchanger, and re-injected at the top of the column.

According to another specific embodiment of the present invention, the reactor used is a jet loop reactor equipped with a heat exchanger between the pump and the ejector.

Advantageously, the compound of formula (I) is added in liquid form. Compounds of formula (I) having a melting point of 10°C or less can be added at a temperature close to room temperature, i.e., 15 to 35°C. Compounds of formula (I) having a melting point above 10°C are preferably heated, for example to a temperature 25°C above their melting point, before being introduced into the reactor. The solvent is preferably introduced into the reactor at a temperature of 5 to 35°C, preferably close to room temperature, i.e., 15 to 35°C.

pressure
The pressure in the reactor during the hydrobromination reaction step (a) is generally between 0.5 and 5, preferably between 0.9 and 3, in particular 1 to 1.5 bar absolute. Advantageously, the reactor is at an absolute pressure of between 1.05 and 1.25 bar absolute.

Advantageously, the equipment provided for carrying out the method comprises at least one gas vent for controlling the pressure. It is thus possible to keep the pressure constant by removing excess gas, in particular non-reactive gaseous compounds introduced by HBr, and HBr that has not dissolved in the reaction medium.

Advantageously, the hydrobromination reaction step (a) of the process of the present invention makes it possible to achieve almost complete conversion of the compound of formula (I) at reduced residence times. The residence time in the reactor is therefore generally between 1 and 60 minutes, preferably between 2 and 45 minutes, preferably between 5 and 30 minutes.

It has been discovered that the hydrobromination process can be carried out using solvents other than toluene and benzene, without a significant decrease in yield, provided that a sufficient content of HBr dissolved in the reaction medium is ensured at the reactor outlet. It has been observed that under these conditions it is possible to obtain high selectivities and therefore high yields of the product of formula (II).

It is of course possible to increase the amount of HBr injected into the reactor until the desired yield is obtained, but this incurs costs associated with producing HBr and removing it from the reaction mixture.

Therefore, according to certain embodiments of the process of the present invention, it is possible to recycle the residual HBr in the reaction mixture withdrawn from the reactor, thereby increasing the molar ratio of HBr injected into the reactor in step (a) without any associated additional costs. The accumulation of recycled residual HBr associated with using HBr in stoichiometric excess allows the concentration of HBr in the reaction medium in step (a) to approach the solubility of HBr in the reaction medium at the temperature and pressure under consideration.

Step (b) of separating the residual HBr from the reaction mixture can be carried out in suitable separation equipment, such as a stirred vessel, an exchanger and a flash drum unit, or even preferably in a column equipped with packing or plates and with a reboiler at the bottom.

The recycling of HBr can be achieved by withdrawing the reaction mixture from the hydrobromination reactor and sending it to a separation device, where the HBr can be separated from the reaction mixture by simple heating. Preferably, the liquid mixture is heated to a temperature close to the boiling point of the solvent so as to evaporate more than 70%, preferably more than 80%, preferably more than 90%, and in particular more than 99% of the residual HBr present in the reaction stream. The gaseous HBr thus recovered can then be returned to the first reactor by conventional means. It also remains within the scope of the present invention if the gas stream resulting from the separation step is cooled, thus inducing at least partial condensation of the solvent entrained in this gas stream, and the gas and liquid streams are returned to step (a).

At the end of this stage of residual HBr separation, a liquid stream of the product of formula (II) and solvent is also recovered. This liquid stream can be subjected to a washing step, for example with water or dilute aqueous sodium hydroxide solution, to remove traces of residual HBr, followed by a separation step by settling. The solvent can be removed, for example by evaporation, and then, if appropriate, recycled to the reaction. The recovered crude product of formula (II) can then be purified by conventional means, in particular by crystallization in the molten state or in particular by recrystallization from the reaction solvent, or can be used directly without a purification step.

According to another specific embodiment of the process of the present invention, at least partial recycling of the HBr present in the gas stream leaving step (a) is achieved by at least partial separation of the HBr contained in the gas stream resulting from the reaction mixture of step (a) and returning the separated HBr to step (a). The gas stream leaving step (a) is advantageously contacted with a solvent, which is optionally recycled, in order to absorb a portion of the HBr. This contacting operation can be carried out by means known to those skilled in the art, for example, a packed column. The solvent stream thus obtained, enriched in HBr, can then be sent to step (a). The stoichiometric excess of HBr introduced into the reaction and the efficiency of its separation in the separation equipment thus make it possible to control the excess of HBr dissolved in the reaction medium in order to optimize the yield of the product of formula (II).

The product of formula (II) can undergo ammonolysis by reaction with ammonia to form the corresponding ω-aminocarboxylic acid or ester of formula (III). The compound of formula (III), optionally after a purification step, can be polymerized, for example by polycondensation, to give the corresponding polyamide. Alternatively, it can be used with other monomers, such as diamines and dicarboxylic acids, one or more lactams, or polyethers, to produce the corresponding copolymer.

The process according to the invention makes it possible to obtain a product of formula (II) containing fewer impurities, thereby simplifying the purification steps before the reaction with ammonia or after the reaction with ammonia if the product is used without purification.

In the embodiment of the continuous process of the invention shown in Figure 1, the hydrobromination reactor (1) comprises a continuous feed (2) of the compound of formula (I), a continuous feed (3) of solvent, a continuous feed (4) of initiator, a continuous feed (5) of gaseous HBr introduced into the process, and a continuous feed (6) of recycled HBr in gaseous form. The reactor further comprises a gas vent (7) making it possible to remove excess gas reaching the reactor. It comprises a liquid withdrawal (8) of the reaction mixture which is sent to an apparatus (9) for the separation of HBr, which comprises a withdrawal (6) of HBr and a withdrawal (10) of the liquid phase containing the compound of formula (II) and the solvent.

In the embodiment of the continuous process of the present invention shown in Figure 2, the hydrobromination reactor (1) comprises a vessel (11) equipped with a recirculation loop (12) having a pump (13), the inlet of which is connected to the vessel (11) and the outlet of which is connected to a heat exchanger (14) connected to a venturi (15) mounted on the reactor. A continuous supply of HBr (5) introduced into the process and a continuous supply of recycled HBr (6), as well as a loop (16) for equilibrating the gaseous headspace of the reactor, are connected to the gas inlet of the venturi. A continuous supply of solvent (2), a continuous supply of compound of formula (I) (3), and a continuous supply of initiator (4) are connected to the line between the heat exchanger and the venturi. The line (8) for liquid withdrawal of the reaction mixture is connected to a vessel (9) for separation of HBr, which is provided with a continuous withdrawal (6) of recycled HBr in gaseous form and a continuous withdrawal (10) of a liquid phase containing the compound of formula (II) and the solvent.

In the embodiment of the continuous process of the present invention shown in Figure 3, the hydrobromination reactor (1) is equipped with a jacketed vessel (11) cooled by a continuous supply (14) of heat exchange fluid and a recirculation loop (12) with a pump (13), the inlet of which is connected to the vessel (11) and the outlet of which is connected to a venturi (15) connected to the reactor. A continuous supply (5) of gaseous HBr introduced into the process and a gaseous form of recycled HBr (6), as well as a loop (16) for equilibrating the gaseous headspace of the reactor, are connected to the gas inlet of the venturi. A continuous supply (2) of a mixture of the compound of formula (I), solvent and initiator is connected to the line between the heat exchanger and the venturi. The line (8) for liquid withdrawal of the reaction mixture is connected to a second jacketed vessel (9) for separation of HBr, which vessel is equipped with a continuous withdrawal (6) of HBr in gaseous form and a continuous withdrawal (10) of the liquid phase containing the compound of formula (II) and the solvent by means of a pump.

The present invention is described in more detail in the following examples.

Example 1
The hydrobromination reaction of 10-undecenoic acid is carried out in the installation shown in Figure 3, which is described below. The venturi (15) is a glass filter pump (Water Jet Pump Reference 181-9205 manufactured by VWR International), the liquid outlet of which is connected to the cylindrical jacketed vessel (11). The recirculation pump (13) has a flow rate of 100 l/h.

A 15% by weight solution of 10-undecenoic acid in cyclohexane at room temperature and an air stream are injected via the feedstock (2) at a flow rate of 2361 g/h. Gaseous HBr is continuously injected into the process at a rate such that the ratio of the gaseous HBr flow rate (mol/h) to the 10-undecenoic acid flow rate (mol/h) is 1.15. The ratio of the volumetric flow rate of HBr to the volumetric flow rate of air is 35:1.

The vessel (11) is maintained at a pressure of 0.1 bar above atmospheric pressure by a vent (7) on the reactor's gas phase, which is connected to the atmosphere by a vent treatment system. Throughout the experiment, the temperature in the vessel (11) is kept constant at 24°C by circulating a heat exchange fluid in the jacket. The volume of the reaction medium in the vessel (11) and loop (12) is kept constant at 0.3 liters by a continuous outlet (8) to the separation vessel (9). The residence time in the first reactor is approximately 6 minutes.

The separation vessel (9) is stirred with a magnetic bar and heated by circulating a heat exchange fluid in the jacket so that the temperature of the reaction mixture is maintained at 80°C. The liquid level in vessel (9) is maintained at 0.15 liters by continuously pumping the reaction mixture using pump (10). At start-up, vessel (11) and the loop contain cyclohexane saturated with HBr, and vessel (9) is empty.

After 60 minutes, an aliquot of the liquid reaction mixture is withdrawn on line (8) and subjected to analysis by silver salt analysis and gas chromatography to determine the concentration of residual HBr at the outlet of the reactor and the performance quality of the hydrobromination reaction.

Silver salt analysis makes it possible to determine the concentration by weight of HBr in an aliquot. This is done by diluting the aliquot 30% with demineralized water, shaking vigorously, and then separating by settling. After that, half of the aqueous phase is withdrawn, diluted 10 times with demineralized water, and titrated with a 0.1N aqueous solution of silver nitrate.

Analysis by gas chromatography is performed by derivatizing 0.1 ml of the liquid reaction mixture with 1 ml of N,O-bis(trimethylsilyl)trifluoroacetamide and 1% trimethylchlorosilane at 80°C for 30 minutes, then injecting it into a non-polar column and detecting it by flame ionization. From the chromatogram, the ratio of the area corresponding to 10-undecenoic acid to the sum of the areas corresponding to compounds with 11 carbon atoms is determined. The conversion rate of 10-undecenoic acid can then be calculated by subtracting this ratio from 1 according to the following formula:
Conversion rate = 1 - (area of 10-undecenoic acid) / (total area).

The yield is then estimated from the chromatogram by determining the ratio of the area corresponding to 11-bromoundecanoic acid in the aliquot to the sum of the areas corresponding to the 11-carbon compounds according to the following formula:
Yield = (area of 11-bromoundecanoic acid) / (total area)

The selectivity can then be estimated according to the following formula: Selectivity = Yield/Conversion.

The analytical results of the aliquots and reaction performance quality are shown in Table 2.

The ratio of the molar flow rate of gaseous HBr injected into the reaction mixture (equal to the sum of the molar flow rate of HBr introduced into the process (5) and the molar flow rate of recycled HBr (6)) to the molar flow rate of 10-undecenoic acid is estimated to be 1.85.

After 65 minutes, an aliquot is withdrawn at the outlet of the separator vessel and subjected to analysis by gas chromatography. The selectivity for 11-bromoundecanoic acid is 95%, thus identical to the selectivity at the outlet of the hydrobromination reactor, and the yield is 94.9%.

Example 2
Example 1 is reproduced using the same equipment, but with the elimination of the second vessel (9) and the vent recirculation line (6). The ratio of the flow rate (mol/h) of gaseous HBr injected into the reaction mixture to the flow rate (mol/h) of 10-undecenoic acid is adjusted to 1.5.

The results are shown in Table 2.

Example 3
Example 2 is reproduced, but the ratio of the flow rate (mol/h) of gaseous HBr injected into the reaction mixture to the flow rate (mol/h) of 10-undecenoic acid is adjusted to a value of 1.4.

The results are shown in Table 2.

Example 4
Example 2 is reproduced, but the ratio of the flow rate (mol/h) of gaseous HBr injected into the reaction mixture to the flow rate (mol/h) of 10-undecenoic acid is adjusted to 1.3.

The results are shown in Table 2.

Example 5
Example 1 is reproduced, but the HBr injected at (5) is replaced by a HBr/hydrogen/HCl mixture in a volume ratio of 90/4/1, and the ratio of the flow rate of 10-undecenoic acid (mol/h) to the flow rate of HBr (without hydrogen or HCl) introduced into the process at (5) is kept at 1.05.

The results are shown in Table 2.

Example 6
Example 1 is reproduced with the following changes:
Instead of injecting a solution of 10-undecenoic acid in cyclohexane in (7), a stream of molten 10-undecenoic acid at 50°C and a stream of methylcyclohexane at room temperature are injected in a weight ratio of 15/85 into the circuit between the discharge port of the pump and the liquid inlet of the venturi.
- The container (11) is maintained at 20°C.
The vessel (9) is replaced by a column adjusted to 100°C and equipped with a packing and a reboiler at the bottom, the liquid stream coming from the vessel is injected at the top, the reaction liquid is withdrawn at the bottom by means of a pump (10) with a liquid volume of 0.06 liters to maintain a constant level in the reboiler, and the gas vent at the top of the column is returned to the gas intake of the venturi.

The results at the reactor outlet are shown in Table 2.

Analysis by silver salt analysis and chromatography makes it possible to show that the liquid reaction mixture at the outlet of pump (12) contains less than 0.1% HBr and that the yield at the outlet of pump (12) is 94.8%.

Example 7
Example 2 is reproduced, but the vessel (11) and the venturi and liquid loop are replaced by a pump with a stirred jacketed vessel equipped with a self-priming turbine. A stream of HBr (5) is fed below the stirring rotor. The ratio of the flow rate (mol/h) of gaseous HBr injected into the reaction mixture to the flow rate (mol/h) of 10-undecenoic acid is adjusted to 1.85, and the temperature in the vessel (11) is maintained at 20°C.

The results are shown in Table 2.

The combined results demonstrate that the hydrobromination reaction can be carried out in solvents different from toluene and benzene by injection of HBr in gaseous form at ambient temperature and short residence times, providing very satisfactory yields.

It is observed that the greater the excess HBr injected into the reaction mixture and the greater the concentration of HBr in the reaction medium leaving the reactor, the better the selectivity.

Furthermore, it has been observed that recycling of HBr allows for a reduction in the flow rate of HBr introduced into the process to achieve high selectivity. Recycling can be provided, for example, by separation equipment and a vent recycle line. More specifically, it is possible to achieve 95% selectivity while operating with a molar excess of HBr of 5 mol% to 15 mol%, whereas in the absence of recycling, HBr must be used in a molar excess of greater than 50%.

Furthermore, it was possible to confirm that in the context of the method of the present invention, it is possible to use HBr with a residual content of hydrogen or HCl without substantially affecting the yield (see Example 5).

Furthermore, it has been found that removing HBr from the reaction mixture using a column with packing and a reboiler at the bottom makes it possible to significantly reduce the residual HBr content without reducing the reaction yield (see Example 6).

Finally, it was determined that the use of other gas-liquid mixers than a venturi, such as a self-priming turbine, could achieve comparable results.

[List of cited references]
FR928265
Semyonov et al. , Maslozhirova Promyshlennost, 1971, Vol. 37, pp. 31-33
CN103804209B
EP3030543B1

Claims (22)

A process for the continuous synthesis of compounds of formula (II) Br—(CH ₂ ) _n+2 —COOR, comprising:
(a) hydrobromination of a compound of formula (I) CH ₂ ═CH—(CH ₂ ) _n —COOR with HBr in the presence of a radical initiator and at least one solvent,
In formulas (I) and (II), n is an integer between 7 and 9, and R is selected from H or a linear or branched alkyl group containing 1 to 10 carbon atoms;
1. A process characterized in that the reaction is carried out in the absence of benzene and toluene, and in step (a), HBr is injected into the reaction mixture in gaseous form and in a stoichiometric excess , and the ratio of the molar flow rate of HBr injected in step (a) to the molar flow rate of the compound of formula (I) injected in step (a) is from 1.3 to 2.2 . 2. The method of claim 1, wherein R is selected from H, methyl, ethyl, isopropyl, or propyl. 3. The method according to claim 1 or 2, characterized in that the ratio of the molar flow rate of HBr injected in step (a) to the molar flow rate of the compound of formula (I) injected in step (a) is 1.4 to 2 . 4. The method according to claim 3, characterized in that the ratio of the molar flow rate of HBr injected in step (a) to the molar flow rate of the compound of formula (I) injected in step (a) is between 1.5 and 1.9. 5. The process according to any one of claims 1 to 4 , characterized in that the outlet stream from the reactor of liquid reaction mixture at the end of step (a) comprises at least 2 wt. % HBr. 6. The process of claim 5, wherein the outlet stream from the reactor of liquid reaction mixture at the end of step (a) comprises at least 3 wt. % HBr. 6. The process of claim 5, wherein the outlet stream from the reactor of liquid reaction mixture at the end of step (a) comprises at least 3.5 wt. % HBr. 6. The process of claim 5, wherein the outlet stream from the reactor of liquid reaction mixture at the end of step (a) comprises at least 4 wt. % HBr. (b) separating excess HBr from the liquid reaction mixture resulting from step (a);
9. The process according to claim 1, further comprising the subsequent steps of: (b1) optionally separating excess HBr from the gaseous reaction mixture resulting from step (a); and (c) recycling the HBr separated in step (b) and, where appropriate, in step ( b1 ) to step (a). (a1) introducing into a first reactor at a suitable temperature and for a suitable residence time the compound of formula (I), HBr, an initiator and one or more solvents; and (a2) withdrawing the reaction mixture from the first reactor and introducing it into a separation device, where appropriate:
10. The process according to claim 1, characterized in that it is followed by the subsequent steps of: (b) separating residual HBr from the reaction mixture; and ( c ) recycling the separated HBr to step (a1). 11. The method according to any one of claims 1 to 10 , characterized in that step (a) is carried out at a temperature between 5°C and 50°C. 12. The method of claim 11, wherein step (a) is carried out at a temperature between 10°C and 40°C. 12. The method of claim 11, wherein step (a) is carried out at a temperature between 20°C and 30°C. 14. The process according to any one of claims 1 to 13 , characterized in that the radical initiator is molecular oxygen, used as such or in a mixture with an inert gas. 15. The method according to claim 14, characterized in that the mixture with an inert gas is air or oxygen-enriched air. 16. The method according to any one of claims 10 to 15 , characterized in that the first reactor is a stirred vessel with a self-priming turbine or a jet loop reactor equipped with a venturi. 17. The method according to any one of claims 10 to 16 , characterized in that the separation device is a stirred vessel or a column. 18. The process according to any one of claims 1 to 17 , characterized in that it is carried out in the absence of an aromatic solvent. 19. A process according to any one of claims 1 to 18 , characterized in that the product of formula (I) is selected from 11-bromoundecanoic acid, 10-bromodecanoic acid and 12-bromododecanoic acid . 20. The process according to any one of claims 1 to 19, characterized in that the solvent is selected from cyclohexane, methylcyclohexane, heptane, methylcyclopentane, n-hexane, 2-methylhexane, 3-methylhexane, n-heptane, isooctane, petroleum ether, tetralin, 1,1,1-trichloroethane, dibromoethane, chloroform, carbon tetrachloride, tetrachloroethylene, 1-bromopropane, dimethyl carbonate, tetrahydrofuran, 1,4-dioxane, 2-methyltetrahydrofuran, tetrahydropyran, 1-propoxypropane, 1 -ethoxybutane, 2-isopropoxypropane, acetonitrile and mixtures thereof. A process for the synthesis of a compound of formula (III) NH ₂ —(CH ₂ ) _n+2 —COOR, comprising the process according to any one of claims 1 to 20,
21. A process comprising the steps of: (i) ammonolysis of the compound of formula (II) obtained by the process according to any one of claims 1 to 20 ; and (ii) isolation of the compound of formula (III) NH ₂ —(CH ₂ ) _n+2 —COOR formed. 22. A process for the synthesis of polyamides or copolyamides, comprising a step of polycondensing a compound of formula (III) obtained by the process according to claim 21 , either alone or in a mixture with other monomers.